A Prospective, Multicenter, Observational Cohort Study of Proton and Proton-Photon Hybrid Partial Stereotactic Ablative Boost Radiotherapy (P-SABR) for Unresectable Large Tumors
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 主要终点
- Incidence of treatment-related adverse events of grade ≥ 3 (CTCAE v5.0)
研究概览
简要总结
This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable larege tumors (longest diameter > 5 cm) who receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons. The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0). Secondary objectives are dosimetric and the 1-year local control rate (RECIST 1.1, in-field). Participants are followed for up to 5 years.
详细描述
BACKGROUND Large tumors (longest diameter > 5 cm) are often unresectable and respond poorly to conventionally fractionated radiotherapy (CFRT) because of their size and hypoxic core, while normal-tissue tolerance prevents delivering stereotactic ablative radiotherapy (SABR) to the whole tumor. Partial stereotactic ablative boost radiotherapy (P-SABR) delivers a SABR boost only to the central part of a large tumor, followed by CFRT to the whole target. Proton beams, with their Bragg-peak dose fall-off, may sharpen this "onion-skin" dose distribution and further increase the biologically effective dose (BED) within the tumor core.
DESIGN This prospective, multicenter, observational cohort study will enroll 60 adults with unresectable bulky tumors (longest diameter > 5 cm) who, as part of routine care, receive one of two treatment modes: (A) proton P-SABR, in which both the proton partial-SABR boost (course 1) and the subsequent proton CFRT (course 2) are delivered at the proton center; or (B) proton-photon hybrid P-SABR, in which course 1 is delivered with protons at the proton center and course 2 CFRT is delivered with photons (IMRT/VMAT) either at the same center or at Peking University First Hospital or one of six photon sub-centers, after central review of the composite plan. Cohort membership follows the patient's own choice and care pathway; the study does not assign treatment or intervene in clinical decisions, and no formal between-cohort hypothesis testing is planned.
OUTCOMES The primary objective is to describe, in each cohort, the incidence of treatment-related grade ≥ 3 acute and late adverse events (CTCAE v5.0). Secondary objectives are dosimetric (percentage of the GTV receiving BED10 ≥ 100 Gy, PTV V95% and V100%, organ-at-risk doses) and the 1-year local control rate (RECIST 1.1, in-field). Participants are followed for up to 5 years.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed malignancy
- •At least one tumor with a longest diameter > 5 cm
- •Not amenable to curative surgical resection, or patient declines surgery, or surgery contraindicated because of medical comorbidities
- •Age ≥ 18 years
- •ECOG performance status 0-2
- •Life expectancy > 3 months
- •Written informed consent
排除标准
- •Prior radiotherapy to the same site
- •Severe cardiopulmonary insufficiency precluding radiotherapy
- •Concurrent other active malignancy
- •Uncontrolled acute infection or bowel obstruction
- •Pregnancy or breastfeeding
- •Intracranial lesion
- •Tumor directly invading the full thickness of the esophageal, gastric or intestinal wall with active ulceration, fistula or uncontrolled risk of perforation (tumors that only abut or displace a hollow organ without full-thickness invasion are not excluded)
- •Uncontrolled active tumor bleeding, or impending pathological fracture requiring orthopedic intervention
- •Any other condition that, in the investigator's judgment, makes the patient unsuitable for the study
研究组 & 干预措施
Cohort A: Proton P-SABR
Participants who receive the entire P-SABR course with protons at Hebei Yizhou Cancer Hospital: course 1, proton partial stereotactic ablative boost (intensity-modulated proton therapy, IMPT); course 2, proton conventionally fractionated radiotherapy (CFRT). Planned enrollment: 30.
干预措施: Proton P-SABR (Radiation)
Cohort B: Proton-Photon Hybrid P-SABR
Participants who receive course 1 (proton partial stereotactic ablative boost, IMPT) at Hebei Yizhou Cancer Hospital, followed by course 2 photon conventionally fractionated radiotherapy (IMRT/VMAT with daily CBCT) delivered either at the same center (pathway A, same-center; planned n = 10) or at Peking University First Hospital or one of six photon sub-centers (pathway B, cross-center; planned n = 20) after central review of the composite plan. Planned enrollment: 30.
干预措施: Proton-Photon Hybrid P-SABR (Radiation)
结局指标
主要结局
Incidence of treatment-related adverse events of grade ≥ 3 (CTCAE v5.0)
时间窗: From the first fraction of radiotherapy to the end of the study
Up to 5 years after completion of radiotherapy (acute events: from the first fraction of radiotherapy through 90 days after completion; late events: from day 91 after completion through 5 years)
次要结局
- Percentage of the gross tumor volume (GTV) receiving a biologically effective dose (BED10) ≥ 100 Gy(Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized))
- Planning target volume (PTV) coverage: V95% and V100%(Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized))
- Doses to organs at risk (OARs)(Up to 3 weeks after the first fraction of radiotherapy (when the composite plan of course 1 and course 2 is finalized))
- 1-year local control (LC) rate(12 months after the first fraction of radiotherapy)
研究者
Xian-shu Gao
Professor and Director, Department of Radiation Oncology
Peking University First Hospital